Introduction It is widely accepted that certain 'high risk' human papillomavirus (HPV) genotypes, particularly HPV 16 and 18 are aetiological agents in the development of neoplasia of the uterine cervix. The long latent period between initial HPV infection and emergence of carcinoma suggests that HPV alone is insufficient for malignant transformation and additional factors are required for the progression of HPV infected cells to a neoplastic phenotype. Cells with integrated HPV express viral E6 and E7 oncoproteins which are crucial for immortalisation of epithelial cells via their action on host p53 protein. It is therefore of particular interest to elucidate the molecular mechanisms that alter the expression of E6/E7 proteins during HPV-associated tumorigenesis. Recently, human herpesvirus-6 (HHV-6) has been shown to infect a HPV-immortalised cervical epithelial cell line and transactivate HPV 18 promoters, upregulating gene expression of E6 and E7 HPV oncoproteins (Chen et al., 1994; DiPaolo et al., 1994). HHV-6, first isolated from peripheral blood mononuclear cells of patients with AIDS and lymphoproliferative disorders, is the causative agent of exanthem subitum, heterophile-negative infectious mononucleosis and other febrile illnesses. HHV-6 has recently been detected in oral carcinomas (Yadav et al., 1994). HHV-6 also contains DNA sequences which can transform epithelial cells in culture.
The present study was undertaken to evaluate the prevalence of HPV in formalin-fixed, paraffin-embedded cervical carcinoma tissues using PCR followed by non-radioactive Southern hybridization with type-specific oligonucleotides for HPV 16 and 18. In addition, the tissue sections were immunohistochemically screened with two monoclonal antibodies, for expression of HPV 16 L1 and HPV 18 E6 proteins. A total of 57 of 60 cervical carcinomas (95.0%) were found with HPV using both techniques. HPV 16 and HPV 18 were present in equal proportions. Results of both DNA hybridization and immunohistochemistry were in agreement for the majority of the cases. HPV 16 and 18 DNA and virus-encoded antigens, L1 and E6 were found highly prevalent in these cervical carcinomas. Due to the high prevalence of HPV with cervical carcinoma in Malaysia, the implementation of routine diagnosis for the virus in cervical biopsies would be clinically useful.
Specific human papillomavirus (HPV) types have been implicated in the development of cervical carcinoma worldwide. Novel molecular techniques have facilitated the detection and typing of HPV in cervical lesions. DNA preparations from a series of 23 histopathologically confirmed cervical carcinoma patients were analyzed by polymerase chain reaction (PCR) using degenerate primers for the presence of HPV DNA sequences. A total of 22 of 23 cases studied (95.7%) were found positive for HPV DNA sequences. Further studies by DNA hybridization with viral specific probe and restriction enzyme analysis demonstrated the presence of HPV 16 in 73.9% (17/23) and HPV 18 in 65.2% (15/23) of the cases examined. Interestingly, the uncommon HPV 31 and 33 were also found but with a lower percentage (16.9%). It was noted that HPV 16 frequency in the carcinoma increased with age but HPV 18 was evenly present at all ages investigated. We found that HPV was frequently associated with the majority of the cervical carcinomas, and in all but one case, oncogenic high risk HPV genotypes were present. We conclude that HPV infection of the genital tract has an important role in the development of the disease in Malaysia.